Method of preparing beta-lactones of 2, 2, 4, 4-tetraalkyl-3-hydroxy-3-butenoic acids by catalyzed reaction of dialkylketenes



United States Patent @hhce 3,062,836 Patented Nov. 6, 1962 3,062,836METHGD F PREPARING fl-LACTONES 9F 2,2, 1,4-

TETRAALKYL-3-HYDROXY-3mJUTENQEfi ACEDS BY CATALYZED REACTIQN @F DHALKYL-KETENEEE James C. Martin, Kingsport, Tenn, assignor to Eastman KodakCompany, Rochester, N.Y., a corporation of New Jersey No Drawing. FiledMay 9, 1961, Ser. No. 108,738

9 Ciaims. (Ci. 260-3419) This invention relates to a novel method forpreparing certain unsaturated B-lactones. More particularly, it relatesto a method of preparing the ,B-lactones of 2,2, 1,4-tetraalkyl-3-hydroxy-3-butenoic acids by the reaction of dialkylketenesin the presence of a Lewis acid as a catalyst.

The production of unsaturated fs-lactones by the method of the inventionis illustrated by the following (Dialkyllretene) (2.2. t aa v1-3-hydroxy-B-butenoic acid B-lactone) wherein R R R and R are the same ordifferent alkyl radicals of from 1 to 4 carbon atoms.

Lactones of the above type are valuable intermediates in the preparationof a number of useful products. For example, when contacted with astrongly basic catalyst such as sodium methoxide in a solvent such asether or benzene they form useful crystalline polymers. They are alsouseful as intermediates in the preparation of valuable alleniccompounds. For instance, tetramethyl allene is produced in good yield bypyrolysis of 2,2,4- trimethyl-3-hydroxy-3-pentenoic acid ,B-lactone at atemperature, e.g., of 450 C. Still further, the lactones are usefulstarting materials in the preparation of tetraalkyl acetoacetic estersby reaction with a hydroxyl compound such as methanol. As chemicalreagents or intermediates the lactones of my invention have importantadvantages over the previously known dialkylketene dimers, i.e., thetetraalkyl-l,3-cyclobutanediones. For example, whiletetramethyl-l,3-cyclobutanedione is a volatile, easily sublimed solid,the isomeric lactone is a liquid at normal temperature and pressure andis, therefore, much more convenient to employ as a reagent.

These lactones are disclosed as novel compounds in the copending US.patent application of Edward U. Elam entitled Unsaturated ,B-Lactonesand Method of Preparing Them, S.N. 108,740, filed on the same day as thepresent application. Elam discloses a method of preparation in which adialkylketene is contacted with a strongly basic polymerization catalystsuch as an alkali metal alkoxide in an inert solvent to obtain a solidpolymer. This polymer is then decomposed by pyrolysis to yield a2,2,4,4-tetraalkyl-3-hydroxy-3-butenoic acid {3- lactone. The methoddisclosed by Elam is a valuable method for producing the lactones but Ihave developed another method whereby lactones of this type can beobtained by the catalytic conversion of dialkylketenes without thenecessity of forming and decomposing a solid polymer.

The method of my invention, in general, comprises contacting adialkylketene, of which the alkyl groups have from 1 to 4 carbon atoms,with a catalytic amount of a Lewis acid such as aluminum chloride andrecovering a reaction product comprising a2,2,4,4-tetraalkyl-3-hydroxy-3-butenoic acid fl-lactone of which thealkyl groups have from 1 to 4 carbon atoms. (The term Lewis acid is usedherein to designate an aprotonic acid of the Lewis type and is describedmore fully hereinafter.)

In preferred modifications of the method the reaction is carried out inthe presence of a solvent having a high dielectric constant and at atemperature in the range of 50-150 C.

It is known in the art that dialkylketenes react with themselves,spontaneously in the case of the lower members such as dimethylketene,to form tetraalkyl-l,3-cyclobutanediones. (Organic Reactions, R. Adams,editor, John Wiley and Sons, N.Y., 1946, vol. III, chap 3, Hanford andSauer, Preparation of Ketenes and Ketene Dimers). In contrast to thisknown reaction I have discovered that in the presence of an aprotonicLewis acid the dialkylketenes can be caused to react with themselves toform 2,2,4,4-tetraalkyl-3-hydroxy-3-butenoic acid [S-lactones. Thestructure of the lactone product obtained by my novel method has beenestablished by three analytical methods: (1) elementary analysis, (2)infrared spectroscopy, and (3) nuclear magnetic resonance spectroscopy.

The starting materials for producing lactones of the formula,

by the method of my invention are disubstituted ketenes of thestructure,

wherein the substituents, R, are alkyl groups of 1 to 4 carbon atoms orare alkylene groups which, with the carbon atom to which they areattached, form a 5 or 6 membered saturated carbocyclic ring. Examplesinclude, dimethylketene, ethylmethylketene, diethylketene,butylethylketene, di-n-propylketene, diisobutylketene, din-butylketeneand carbocyclic ketenes such as tetramethyleneketene andpentamethyleneketene. For convenience, I use the term dialkylketene todesignate all of such disubstituted ketenes. The dialkylketenes can beprepared by the method described in copending application of R. H. HaSekand E. U. Elam, S.N. 841,961, filed September 24, 1959.

The reaction can be carried out in the absence of a solvent butpreferably is carried out in the presence of a solvent. The use of asolvent facilitates contact between the catalyst and the startingmaterial and aids in temperature control. The solvent should be inert orat least should not react rapidly with the dialkylketene or the productand should not inactivate the catalyst. Suit able solvents include, forexample, aliphatic and aromatic hydrocarbons, chlorinated aliphatic andaromatic hydrocarbons, esters, dimethylformamide, dimethylacetamide,dimethylsulfoxide, etc. A particularly good solvent is the2,2,4,4-tetraalkyl-3-hydroxy-3-butenoic acid ,B-lactone itself.

My work indicates that the rate of reaction in the method of theinvention is dependent at least in part on the dielectric constant ofthe solvent. For instance, the reaction rate appears to be higher whenthe solvent is acetonitrile (high dielectric constant) than when thesolvent is chloroform, which has a considerably lower dielectricconstant. With the lower dialkylketenes the rate is quite rapid even insolvents such as chloroform. However, based on the discovery that therate of reaction is influenced by the nature of the solvent, a preferredembodiment of the method, particularly when the starting material is adialkylketene of which the alkyl groups have at least 3 carbon atoms,comprises carrying out the reaction in the presence of an inert solventhaving a dielectric constant, measured at 20 C. using a frequency offrom 20 to 20,000 cycles per second, of at least 10.

The reaction can be carried out in the absence of a 3 solvent simply bymixing the Lewis acid with the dialkylketene. If no solvent is used thepurification of the product is simplified.

The molar ratio of the Lewis acid to the dialkylketene can vary fromabout 0.01 to 0.521. The higher ratios give no particular advantage overthe lower ones except in overcoming the effect of small concentrationsof protonic contaminants.

The dimerization of the lower dialkylketenes in the presence of anaprotonie Lewis acid is quite exothermic and extensive cooling is neededto avoid excessive temperatures. The reaction can be carried out attemperatures as low as room temperature but for satisfactory reactionrate the temperature should be at least about C. Preferably, thetemperature is about to C. for reacting the lower dialkylketenes (i.e.,C -C alkyl groups) although higher temperatures are satisfactory. Forthe higher dialkylketenes, i.e., C -C, alkyl groups, the preferredreaction temperature is 69 to C. Temperatures above about C. are lessatisfactory because pressure vessels are required if the temperature isabove the boiling point of the product. Temperatures as high as about300 C. can he used but higher temperatures should be avoided so as toavoid decomposing the lactone product.

The time of reaction depends upon the particular Lewis acid employed andthe reaction temperature. With a high temperature and a strong Lewisacid, the reaction is complete within a few minutes. With lowtemperature or a weak Lewis acid the time required may vary from a fewhours to several weeks.

As I have indicated, the present invention is based on my discovery thataprotonic acids of the Lewis type catalyze the conversion ofdialkylketenes to 2,2,4,4-tetraalkyl- 3-hydroxy-3-butenoic acidB-lactones. As defined by G. N. Lewis, [Valence and the Structure ofAtoms and Molecules, Chemical Catalogue Co., N.Y., 1923; 1. FranklinInst. 226, 243 (1938)] an acid is a substance that can accept a pair ofelectrons from another substance to form a chemical bond. Lewis broaddefinition includes substances that are proton donors, such ahydrochloric acid, and substances that accept electrons but do notfurnish protons, for instance, boron trifluoride. Acids that donateprotons are designated as protonic. Those that merely accept electronsbut do not donate protons are called aprotonic.

The latter type of acids is referred to in this specification as anaprotonic Lewis acid or simply as a Lewis acid. I use these terms todistinguish from the protonic acids or so-called Bronsted acids. Onlyaprotonic Lewis acids are suitable in the method of the invention.Protonic acids are unsuitable. They either fail to achieve conversion ofthe dialkylketene or cause the formation of products other than thedesired lactones. Certain solvents are also unsuitable because they havean available proton. Such unsuitable solvents include water, alcoholsand amines. However, the presence of a small amount of an unsuitablesolvent such as water in a satisfactory solvent such as heptane can beovercome by the use of a sufficient amount of the anhydrous Lewis acid.

A large number of the described aprotonic acids of the Lewis type asused in the method of the invention are available. They include suchmaterials as boron trifluoride, silicon tetrachloride, phosphorouspentoxide, sulfur dioxide, aluminum chloride, antimony pentachloride,ferric chloride, stannic chloride, boron trifiuoride, titaniumtetrachloride, zinc bromide, zinc chloride, etc. The wellknownFriedel-Crafts catalysts, a number of which are mentioned, comprise aclass of aprotonic Lewis acids that are particularly valuable ascatalysts in the method of my invention.

Further understanding of the invention can be obtained from the examplesfollowing, which illustrate certain principles of the invention. T hefirst example demonstrates the conversion of dimethylketene to2,2,4,4-tri- 4. methyl-3-hydroxy-3-butenoic acid fi-lactone, usingaluminum chloride as the Lewis acid catalyst and using the lactoneproduct as the reaction solvent.

Example 1.-To a stirred solution of 3 g. of aluminum chloride in 82 g.of 2,2,4-trimethyl-3-hydroxy-3-pentenoic acid, [i-lactone under nitrogenwas added 70 g. of dimethylketene. The reaction was quite exothermic andthe temperature was kept in the range 40-70 C. by an ice bath around thereaction vessel. The reaction was over in a few minutes, but thestirring was continued for an additional hour. The reaction solution wasexamined by gas chromatography. The chromatogram contained only onepeak; this was identified as 2,2,4-trimethyl-3- hydroxy-B-pentenoicacid, [3-lactone. Distillation through a 6-in. Vigreux column gave 145g. of 2,2,4-trimethyl-3- hydroxy-3-pentenoic acid fl-lactone, Bl. 8385C. (40 mm.), 1.438 Analysis-Called. for C3H12O2Z C, 68-5; H, 8.6; sapon.equiv., 142.2. Found: C, 68.4; H, 8.7; sapon. equiv, 140.0.

The next example demonstrates that a Bronsted or protonic acid will notcatalyze the conversion of dimethylketene to2,2,4-trimethyl-3-hydroxy-3-pentenoic acid f3- lactone.

Example 2.To a stirred solution of 1 g. of p-toluenesulfonic acid in 125ml. of chloroform was added 40 g. of dimethylketene. The solution wasstirred for several hours until all of the dimethylltetene had reacted.Examination of the reaction solution by gas chromatography showed onlychloroform and tetramethyl-l,S-cyciobutanedione.

The following example demonstrates that with no catalyst present,dimethylketene was converted to the normal dimer,tetramethyl-LS-cyclohutanedione.

xample 5.-40 g. of dimethylltetene was added to 125 ml. of chloroform asdescribed in Example 2. All of the dimethylketene was converted totetramethyl-l,3-cyclobutanedione, as determined by gas chromatography.

The next example demonstrates successful practice of the method of theinvention, using the same solvent, i.c., chloroform, as used in theunsuccessful operations of Examples 2 and 3.

Example 4.To a stirred solution of 1 g. of aluminum chloride in 125 ml.of chloroform was added 40 g. of dimethy ltetene. An immediate,exothermic reaction took place, causing the chloroform to reflux. Thereaction was complete in a few minutes. Examination of the reactionsolution by gas chromatography showed only chloroform and2,2,4-trimethyl-3-hydroxy-3-pentenoic acid lactone.

The following example demonstrates the method of the invention, using adifferent dialkylltetene as the starting material.

Example 5 .To a stirred solution of 2 g. of aluminum chloride in 200 ml.of chloroform was added slowly 68 g. of ethylmethylketene. An immediate,exothermic reaction took place causing the chloroform to reflux.Examination of the reaction solution by gas chromatography showed onlychloroform and one other peak. Subse quent distillation yielded aliquid, B.P. 82.84" (11 mm), 11, 1.4448, identified as2,4-dimethyl-2-ethyl-3-hydroxy- 3-hexenoic acid ,B-lactone.

The next example demonstrates the use of still another dialkylketene,namely, butylethylketene, as the starting material in the method of theinvention and the use of the lactone product as the reaction solvent.

Exmnp!e 6.To a stirred solution of 2 g. of stannic chloride in 100 g. of2-butyl-2,4-diethyl-3-hydroxy-3- octenoic acid fi-lactone at 100 C. wasadded 63 g. of butylethylketene. The temperature was kept in the range100120 C. for 15 min. Distillation through a 6-in. Vigreux column gave141 g. of 2-butyl-2,4-diethyl-3-hydroxy-3'octenoic aci ,B-lactone, B.P.104-106 C. (3 mm.).

The next example demonstrates the use in the method 5 of the inventionof a preferred type of reaction solvent having a high dielectricconstant.

Example 7.To a refluxing solution of 2.5 g. of titanium tetrachloride in200 ml. of acetonitrile was added 120 g. of diethylketene. Distillationof the reaction mixture gave 91.2 g. of2,2,4-triethyl-3-hydroxy-3-hexenoic acid ,B-lactone.

Although the invention has been described in considerable detail withreference to certain preferred embodiments thereof, it will beunderstood that variations and modifications can be etfected within thespirit and scope of the invention as described hereinabove and asdefined in the appended claims.

I claim:

1. The method which comprises contacting with a catalytic amount of anaprotonic Lewis acid a disubstituted ketene of the structure,

R R(i ==0 wherein the substituents, R, are selected from the groupconsisting of alkyl groups of from 1 to 4 carbon atoms and alkylenegroups which, together with the carbon atom to which they are attached,form a saturated carbocyclic ring of 5 to 6 carbon atoms, and recoveringas product a lactone of the structure,

R R R R-o=o oo=0 2. The method of preparing a2,2,4,4-tetraalkyl-3-hydroxy-B-butenoic acid Si-lactone which comprisescontacting with a catalytic amount of an aprotonic Lewis acid adialkylketene of which the alkyl groups have from 1 to 4 carbon atoms ata temperature of about 40 to 300 C. and recovering such lactone asproduct.

3. The method of preparing a 2,2,4,4-tetraalkyl-3-hydroxy-3-butenoicacid fi-lactone which comprises forming a mixture consisting essentiallyof dialkylketene of which the alkyl groups have from 1 to 4 carbon atomsand a catalytic amount of an aprotonic Lewis acid, maintaining thereaction mixture at a temperature of about 40 to 300 C., distilling theresulting reaction product and recovering a distillate comprising saidlactone.

4. The method of preparing a 2,2,4,4-tetraalkyl-3-hydroxy-3-butenoicacid B-lactone which comprises forming a reaction mixture comprising adialkylketene of which the alkyl groups have from 1 to 4 carbon atoms,an inert solvent, and an aprotonic Lewis acid in the amount of 0.01 to0.5 :1 mol per mol of dialkylketene, maintaining said reaction mixtureat a temperature of about 40 to 300 C. and recovering a reaction productcomprising said lactone.

5. The method which comprises forming a reaction mixture ofdimethylketene and a catalytic amount of aluminum chloride, maintainingthe reaction mixture at a temperature of about to C. and recovering a reaction product comprising 2,2,4-trimethyl-3-hydroxy-3- pentenoic acidB-lactone.

6. The method which comprises forming a reaction mixture ofmethylethylketene and a catalytic amount of aluminum chloride,maintaining the reaction mixture at a temperature of about 50 to 80 C.and recovering a reaction product comprising the S-lactone of2,4-dimethyl-2-ethyl-3-hydroxy-3-hexenoic acid.

7. The method of preparing 2,2,4-trimethyl-3-hydroxy- 3-butenoic acidfl-lactone which comprises forming a reaction mixture comprisingdimethylketene, said lactone and a catalytic amount of an aprotonicLewis acid, maintaining the reaction mixture at a temperature of about50 to C. and recovering a reaction product comprising said lactone.

8. The method which comprises forming a reaction mixture of adialkylketene, of which the alkyl groups have from 3 to 4 carbon atoms,a catalytic amount of an aprotonic Lewis acid and an inert solventhaving a dielectric constant, measured at 20 C. using a frequency offrom 20 to 20,000 cycles per second, of at least 10, maintaining thereaction mixture at a temperature of about 60 to 150 C. and recovering areaction product comprising a 2,2,4,4-tetraalkyl-3-hydroxy-3=butenoicacid fi-lactone of which the alkyl groups have 3 to 4 carbon atoms.

9. The method of preparing a 2,2,4,4-tetraalkyl-3-hydroxy-3-butenoicacid fl-lactone which comprises contacting with an aprotonicFriedel-Crafts catalyst a dialkylketene of which the alkyl groups havefrom 1 to 4 carbon atoms at a temperature of about 40 to 300 C. andrecovering such lactone as product.

References Cited in the file of this patent Adams (Ed.): OrganicReactions, John Wiley and Sons, New York (1946), page 127.

1. THE METHOD WHICH COMPRISES CONTACTING WITH A CATALYTIC ANOUNT OF ANAPROTONIC LEWIS ACID A DISUBSTITUTED KETENE OF THE STRUCTURE,